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CONGENITAL FACTOR VII DEFICIENCY AND CEREBROVASCULAR STROKE
1006 These factors must provide the most acceptable explanation for the similar but earlier trend in Britain. The UK mortality rate fell from 67 to 32 per million between 1901 and 1932, and this trend continued throughout the period when antibiotics were introduced.2 Despite ignorance of the pathogenesis of rheumatic fever, its association with a combination of pharyngitis, overcrowding, and high population turnover had been described as
3 early as 1930.3 The pathogenicity of Streptococcus pyogenes may have fallen, possibly as a result of exposure to commonly used antimicrobial agents. This may explain the selection of certain M serotypes in Japan, where erythromycin is used to excess for pharyngitis. It is true that a radical preventive approach is required to control
rheumatic carditis. But since both indiscriminate antibiotic prophylaxis and multivalent vaccines are likely to remain impracticable for the foreseeable future, the mainstay of prevention must still be the improvement of the human environment wherever there is overcrowding and a rapidly changing population. Department of Microbiology,
was increased with normal maturation of the series. After 2 weeks the prednisone dosage was gradually reduced to 10 mg a day. Erythropoiesis returned. 6 weeks after the discontinuation of sulphasalazine the blood count was normal and 5-ASA 400 mg twice daily was started, prednisone being withdrawn over 8 weeks. The blood count was normal at 4 and 13 weeks and the patient has remained symptom-free. This patient had an acute pure-red-cell aplasia.33 The prompt correction of anaemia after discontinuation of sulphasalazine and the absence of other factors known to cause this abnormality33 suggest that sulphasalazine was the cause of the selective blood marrow failure. In one other published case of pure-red-cell aplasia associated with sulphasalazinel the anaemia developed during 6 weeks of sulphasalazine therapy at 3 g a day and remitted rapidly on withdrawal of the drug. Combined selective erythroid and megakaryocytic aplasia after sulphasalazine have been observed in one patient. Our patient tolerated 5-ASA well, suggesting that the sulphapyridine moiety had been responsible for the haematological active moiety of toxicity. 5-ASA is thought to be the in bowel and this active disease, sulphasalazine inflammatory principle should be used to avoid the side-effects of sulphasalazine.
therapeutically
University of Leeds, Old Medical School, Leeds LS2 9JT
proportion of granulocytopoiesis
TIMOTHY J. J. INGLIS
1. Chief Medical Officer Acute rheumatism On the state of the public health. London: HM Stationery Office, 1931. 105-14. 2 Chief Medical Officer. Acute rheumatism The Report of the Ministry of Health. London HM Stationery Office, 1949 67-71. 3 Glover JA. On the incidence of rheumatic diseases. Lancet 1930, i: 499-505 4 Stollerman GH. Global changes in group A streptococcal diseases and strategies for their prevention. Adv Intern Med 1982, 27: 373-406.
Third
Department of Medicine, University of Helsinki, Helsinki 00290, Finland
SIR,-Haematological adverse effects (usually haemolytic leucopenia, thrombocytopenia, or aplastic anaemia) have been reported in patients treated with sulphasalazine. Pure-red-cell anaemia, however, has been described in only one case.I Sulphasalazine is split by gut bacteria in the colon to sulphapyridine and 5-aminosalicylic acid (5-ASA). The sulpha moiety has been accused of causing the adverse effects whereas the therapeutic effects of sulphasalazine in inflammatory bowel disease have been ascribed to 5-ASA.’ We describe a patient with pure-red-cell aplasia after treatment with sulphasalazine who, after recovery, was successfully treated with 5-ASA. A 30-year-old woman with a history ofulcerative colitis diagnosed
AM, Kerr GD Pure-red-cell aplasia associated with sulphasalazine. Lancet 1981; ii: 1288. Klotz U, Maier K, Fischer C, Heinkel K. Therapeutic efficacy of sulfasalazine and its
1 Dunn 2.
PURE-RED-CELL APLASIA ASSOCIATED WITH SULPHASALAZINE BUT NOT 5-AMINOSALICYLIC ACID
PEKKA M. ANTTILA MATTI VÄLIMÄKI PERTTI J. PENTIKÄINEN
metabolites
in
patients with ulcerative colitis and Crohn’s disease.
N Engl J Med
1980; 303: 1499-502. 3. Wintrobe MM, Lee GR, Boggs DR, et al, eds Clinical hematology. Philadelphia: Lea
and Febiger,
1981: 724-25.
GE, Palek J. Selective erythroid and megakaryocytic aplasia after sulfasalazine administration. Arch Intern Med 1980, 140: 1122.
4. Davies
anaemia,
the age of 9 was at first treated with a short course of sulphasalazine, whereafter she remained symptomless and no drugs were used. In November, 1984, colonoscopy, done because of reactivation of the disease, revealed chronic ulcerative colitis. Sulphasalazine 1 g three times a day was started, with prednisone 20 mg daily. Erythromycin 500 mg three times a day for 2 weeks was given for a Campylabaeter jejuni infection. 1 month after she started this treatment her haemoglobin was 12 g/dl. After 2 months of treatment she felt tired and 3 weeks later she contacted her doctor because of shortness of breath. She was still taking sulphasalazine 3 g daily and her prednisone dose was 2 - 5 mg every other day. Her haemoglobin level was 4 - 6 g/dl, and she was admitted to Helsinki University Central Hospital. Sulphasalazine was withdrawn and the prednisone was increased to 80 mg a day. Two units of red blood cells were transfused. Before the transfusion the serum lactate dehydrogenase level was 382 U/1, serum haptoglobin was below 0’ 2 g/1, the plasma haemoglobin level was 25 mg/1, and serum total bilirubin level was 8 mmol/1. The presence of autoagglutinins prevented interpretation of the direct Coombs’ test but 1 week, later it was negative. Antinuclear antibodies were negative. On chest X-ray no evidence for thymoma was found. On the second day the haemoglobin concentration was 6-77 g/dl, white cell count 4-4xlO’’/I (neutrophils 64%, lymphocytes 33%, basophilic cells 3%), platelet count 181 x 109/1, at
erythrocyte count 2-18x 10’/l(reticulocytes 0-01%). On the third day, bone marrow aspiration revealed a pure-red-cell aplasia. The marrow was normocellular with no evidence of erythropoiesis. Megakaryocytes were normal; the relative
CONGENITAL FACTOR VII DEFICIENCY AND CEREBROVASCULAR STROKE
SIR,-Congenital deficiency of coagulation factor VII (proconvertin) may be associated with haemorrhage but few cases of deep-vein1-3 thrombosis or pulmonary embolism have been reported. We describe here a case of a vascular stroke in a patient with proconvertin deficiency. This 64-year-old woman had her congenital deficiency of factor VII:C (table) diagnosed by chance. She had no history of haemorrhage or bruising; she had had uncomplicated tooth extractions, and her menstrual periods and deliveries had been normal. Her medical history was unremarkable except for high blood pressure (well controlled by altizide, spironolactone, and clonidine) and arthritis of the neck treated occasionally with aspirin. On Sept 29, 1983, she had a left-sided hemiparesis and was given dipyridamole. After 48 h she had recovered but examination revealed a right cervical murmur associated with mild stenosis of the right brachiocephalic arterial trunk. Echocardiography; Holter monitoring, and a cerebral scan were normal. Dipyridamole was continued, but on May 3, 1984, she had a further left-sided hemiparesis with altered consciousness. This disappeared in 10 days. Angiography demonstrated an atherosclerotic lesion 2 cm long with 20-30% stenosis at the origin of the brachiocephalic trunk. Treatment with flurbinprofen (100 mg per day) began on June 6, but because of side-effects it was replaced by aspirin (100 mg per day) on June 25. The Ivy bleeding-time was 10 min (normal 4-8 min) and the patient has been symptomless for 9 months. Her one brother is also factor VII deficient (10% of normal). Her three children are alive and well and there is no evidence of consanguinity in her family (a common finding in factor VII deficiency). Factor VII is a vitamin-K-dependent clotting factor. In the presence of tissue thromboplastin, activated proconvertin catalyses activation of the factor-X/factor-V/calcium/phospholipid complex. Factor VII deficiency is an autosomal recessive trait4 and is suspected if the prothrombin time is abnormal while the activated partial prothrombin time (APPT) is normal. These tests confirm the
1007 .TESTS OF HAEMOSTASIS
*Adrenahne induced
(May 5) and arachidonic acid induced (July 2). tBovme thromboplastin. tamidolytic method.
the intrinsic coagulation pathway and an abnormality of the extrinsic pathway. A functional assay for factor VII confirms the diagnosis. A very low level of factor VII prolongs the prothrombin time to within a range considered therapeutically desirable in the clinical use of vitamin K antagonists. Such a level would be expected to prevent thrombosis. However, deep-vein thrombosis and pulmonary emboli have been reported in patients with factor VII despite proconvertin levels as low as 14%,35%1, and less 5 than Our patient had two cerebrovascular strokes 6 months apart. These resolved completely and were presumably related to platelet emboli from an atheromatous plaque. Congenital deficiency of antithrombin III (100%) and protein C (94%) were ruled out. Venous thrombosis seems incompatible with a major coagulation factor defect but arterial thrombosis may not be prevented by a coagulation deficiency; rare cases of myocardial infarction have been reported in haemophiliacs.In atherogenesis coagulation may have a minor role compared with that of platelets. Aspirin therapy in such a patient may seem hazardous. Nevertheless, the risk of further cerebrovascular accidents in this patient cannot be ignored, and the normal Duke and only slightly prolonged Ivy bleeding times (table) when the patient was taking 100 mg aspirin daily are
integrity of
deficiency, 3%.
reassuring. JEAN-JACQUES LEFRERE Central Haematology
Laboratory,
Hôtel-Dieu, Paris; and Neurology Service,
Hôpital de la Pitié-Salpétrière, Paris
MARIE-PIERRE CHAUNU
JACQUELINE CONARD MARIE-HELENE HORELLOU MEYER SAMAMA
E, Gude JK Deep vein thrombosis and pulmonary embolism in congenital factor VII deficiency N Engl J Med 1973; 228: 141-42. Godal HC, Madsen K, Nissen-Meyer R. Thrombo-embolism in patients with total proconvertin (factor VII) deficiency. Acta Med Scand 1962; 171: 325-27. Shifter T, Mactey I, Creter D. Thromboembolism in congenital factor VII deficiency. Acta Haematol 1984; 71: 60-62. Mammen EF. Factor VII abnormalities. Sem Thrombos Hemost 1983; 9: 10-21. Hall CA, Rapaport SI, Ames SB, Degroot JA. A clinical and family study of hereditary proconvertin (Factor VII) deficiency Am J Med 1964; 37: 172-81. Borchgrevink CF. Myocardial infarction m a haemophiliac. Lancet 1959; i: 1229-30.
1. Gershwin 2. 3 4 5. 6
From 1964 to 1975, 200 patients were started on maintenance haemodialysis at this hospital,2 of whom 62 are known to be alive (29 on haemodialysis and 33 with a functioning renal transplant). Of these 62 patients, 3 have had severe calcific aortic stenosis. Patient 1 is a 57-year-old man who has been on haemodialysis for 12 years. 1 year ago he had worsening angina of effort associated with signs of significant aortic stenosis. Cardiac catheterisation revealed severe calcific aortic stenosis with minimal aortic regurgitation. 6 months ago an aortic valve was replaced and a heavily calcified tricuspid aortic valve of normal configuration was excised. He is currently well on twice weekly haemodialysis. Patient 2 is a 45-year-old man who started haemodialysis in 1973 for CRF due to chronic glomerulonephritis. In 1975 he received a renal transplant, but 6 months later was put back on haemodialysis. In 1978 signs of mild aortic stenosis were noted and 5 years later a two-dimensional echocardiogram revealed a calcified tricuspid aortic valve with slight calcification of the mitral valve annulus. Cardiac catheterisation in 1983 demonstrated calcific aortic stenosis with a gradient of 60 mm Hg across the valve. He is awaiting aortic valve replacement. Patient3 is a 53-year-old man who began haemodialysis in 1973 and received a successful renal transplant 2 years later. Renal transplant function was good until 1978, but has since gradually declined because of chronic rejection (current EDTA clearance 7 ml/min). In 1978 an aortic systolic murmur was noted and in 1981 an echocardiogram demonstrated aortic-valve calcification and’ thickened valve cusps with mild stenosis. In early 1985 cardiac catheterisation demonstrated severe calcific aortic stenosis, and shortly afterwards an aortic valve was successfully replaced. The aortic valve was tricuspid and appeared normal except for dense calcific deposits on the cusps. Calcification of a tricuspid aortic valve without inflammatory changes is usually seen in elderly patients.3 Our three patients had isolated aortic stenosis, with extracardiac metastatic calcification (periarticular in one and vascular in all three) and no history of rheumatic fever. Although these unusual findings might have occurred by chance an alternative interpretation is that the abnormal calcium-phosphate metabolism seen in CRF resulted in aortic-valve calcification (or accelerated the calcification of a susceptible valve). Mitral annulus calcification in haemodialysis patients has been linked with secondary hyperparathyroidism (two of our patients had had a parathyroidectomy), and aortic valve cusp thickening is more common in haemodialysis patients with mitral annulus calcification than in those without.’1 Since many haemodialysis patients have systolic murmurs, we may have underestimated the incidence of aortic-valvedisease in our haemodialysis patients, and a prospective echocardiographic study will be needed to determine if there is a real association between aortic-valve calcification and CRF. Department of Medicine, Charing Cross Hospital,
E. R. MAHER
London W6 8RF
J. R. CURTIS
MB, Virmani R, Robertson RM, Stone WJ. Mitral annular calcification in chronic renal failure. Chest 1984, 85: 367-71. 2. Henari FZ, Gower PE, Curtis JR, et al. Survival in 200 patients treated by HD and renal transplantation. Br Med J 1977; i: 409-12. 3. Pomerance A. Pathogenesis of aortic stenosis and relation to age. Br Heart J 1972; 34: 569-74 1. Forman
CALCIFIC AORTIC STENOSIS IN CHRONIC RENAL FAILURE
MAGNETIC RESONANCE IMAGING TO DETECT DEEP BASAL GANGLIA LESIONS IN HEMIDYSTONIA THAT ARE MISSED BY COMPUTERISED TOMOGRAPHY
SiR,-Your Sept 14 editorial suggests that some disorders may be associated with premature valve calcification and thus valve stenosis. Calcification of the mitral valve annulus is common in patients with chronic renal failure (CRF), occurs at a younger age than usual, and may cause functional mitral stenosis or regurgitation.’ Aortic-valve calcification is not recognised as a complication of CRF, but we have noted an unusual frequency of calcific aortic stenosis in patients with long-standing renal failure.
SIR,-Hemidystonia is often associated with computerised tomographic (CT) evidence of a lesion such as tumour, infarction, or haemorrhage in the contralateral basal ganglia and/or thalamus.l-4 However, even the most advanced CT scanner may fail to demonstrate a structural lesion in some cases of hemidystonia, even when secondary dystonia is suggested clinically. We describe here one patient in whom magnetic resonance imaging (MRI) demonstrated a large abnormality not visible on a CT scan.
3 early as 1930.3 The pathogenicity of Streptococcus pyogenes may have fallen, possibly as a result of exposure to commonly used antimicrobial agents. This may explain the selection of certain M serotypes in Japan, where erythromycin is used to excess for pharyngitis. It is true that a radical preventive approach is required to control
rheumatic carditis. But since both indiscriminate antibiotic prophylaxis and multivalent vaccines are likely to remain impracticable for the foreseeable future, the mainstay of prevention must still be the improvement of the human environment wherever there is overcrowding and a rapidly changing population. Department of Microbiology,
was increased with normal maturation of the series. After 2 weeks the prednisone dosage was gradually reduced to 10 mg a day. Erythropoiesis returned. 6 weeks after the discontinuation of sulphasalazine the blood count was normal and 5-ASA 400 mg twice daily was started, prednisone being withdrawn over 8 weeks. The blood count was normal at 4 and 13 weeks and the patient has remained symptom-free. This patient had an acute pure-red-cell aplasia.33 The prompt correction of anaemia after discontinuation of sulphasalazine and the absence of other factors known to cause this abnormality33 suggest that sulphasalazine was the cause of the selective blood marrow failure. In one other published case of pure-red-cell aplasia associated with sulphasalazinel the anaemia developed during 6 weeks of sulphasalazine therapy at 3 g a day and remitted rapidly on withdrawal of the drug. Combined selective erythroid and megakaryocytic aplasia after sulphasalazine have been observed in one patient. Our patient tolerated 5-ASA well, suggesting that the sulphapyridine moiety had been responsible for the haematological active moiety of toxicity. 5-ASA is thought to be the in bowel and this active disease, sulphasalazine inflammatory principle should be used to avoid the side-effects of sulphasalazine.
therapeutically
University of Leeds, Old Medical School, Leeds LS2 9JT
proportion of granulocytopoiesis
TIMOTHY J. J. INGLIS
1. Chief Medical Officer Acute rheumatism On the state of the public health. London: HM Stationery Office, 1931. 105-14. 2 Chief Medical Officer. Acute rheumatism The Report of the Ministry of Health. London HM Stationery Office, 1949 67-71. 3 Glover JA. On the incidence of rheumatic diseases. Lancet 1930, i: 499-505 4 Stollerman GH. Global changes in group A streptococcal diseases and strategies for their prevention. Adv Intern Med 1982, 27: 373-406.
Third
Department of Medicine, University of Helsinki, Helsinki 00290, Finland
SIR,-Haematological adverse effects (usually haemolytic leucopenia, thrombocytopenia, or aplastic anaemia) have been reported in patients treated with sulphasalazine. Pure-red-cell anaemia, however, has been described in only one case.I Sulphasalazine is split by gut bacteria in the colon to sulphapyridine and 5-aminosalicylic acid (5-ASA). The sulpha moiety has been accused of causing the adverse effects whereas the therapeutic effects of sulphasalazine in inflammatory bowel disease have been ascribed to 5-ASA.’ We describe a patient with pure-red-cell aplasia after treatment with sulphasalazine who, after recovery, was successfully treated with 5-ASA. A 30-year-old woman with a history ofulcerative colitis diagnosed
AM, Kerr GD Pure-red-cell aplasia associated with sulphasalazine. Lancet 1981; ii: 1288. Klotz U, Maier K, Fischer C, Heinkel K. Therapeutic efficacy of sulfasalazine and its
1 Dunn 2.
PURE-RED-CELL APLASIA ASSOCIATED WITH SULPHASALAZINE BUT NOT 5-AMINOSALICYLIC ACID
PEKKA M. ANTTILA MATTI VÄLIMÄKI PERTTI J. PENTIKÄINEN
metabolites
in
patients with ulcerative colitis and Crohn’s disease.
N Engl J Med
1980; 303: 1499-502. 3. Wintrobe MM, Lee GR, Boggs DR, et al, eds Clinical hematology. Philadelphia: Lea
and Febiger,
1981: 724-25.
GE, Palek J. Selective erythroid and megakaryocytic aplasia after sulfasalazine administration. Arch Intern Med 1980, 140: 1122.
4. Davies
anaemia,
the age of 9 was at first treated with a short course of sulphasalazine, whereafter she remained symptomless and no drugs were used. In November, 1984, colonoscopy, done because of reactivation of the disease, revealed chronic ulcerative colitis. Sulphasalazine 1 g three times a day was started, with prednisone 20 mg daily. Erythromycin 500 mg three times a day for 2 weeks was given for a Campylabaeter jejuni infection. 1 month after she started this treatment her haemoglobin was 12 g/dl. After 2 months of treatment she felt tired and 3 weeks later she contacted her doctor because of shortness of breath. She was still taking sulphasalazine 3 g daily and her prednisone dose was 2 - 5 mg every other day. Her haemoglobin level was 4 - 6 g/dl, and she was admitted to Helsinki University Central Hospital. Sulphasalazine was withdrawn and the prednisone was increased to 80 mg a day. Two units of red blood cells were transfused. Before the transfusion the serum lactate dehydrogenase level was 382 U/1, serum haptoglobin was below 0’ 2 g/1, the plasma haemoglobin level was 25 mg/1, and serum total bilirubin level was 8 mmol/1. The presence of autoagglutinins prevented interpretation of the direct Coombs’ test but 1 week, later it was negative. Antinuclear antibodies were negative. On chest X-ray no evidence for thymoma was found. On the second day the haemoglobin concentration was 6-77 g/dl, white cell count 4-4xlO’’/I (neutrophils 64%, lymphocytes 33%, basophilic cells 3%), platelet count 181 x 109/1, at
erythrocyte count 2-18x 10’/l(reticulocytes 0-01%). On the third day, bone marrow aspiration revealed a pure-red-cell aplasia. The marrow was normocellular with no evidence of erythropoiesis. Megakaryocytes were normal; the relative
CONGENITAL FACTOR VII DEFICIENCY AND CEREBROVASCULAR STROKE
SIR,-Congenital deficiency of coagulation factor VII (proconvertin) may be associated with haemorrhage but few cases of deep-vein1-3 thrombosis or pulmonary embolism have been reported. We describe here a case of a vascular stroke in a patient with proconvertin deficiency. This 64-year-old woman had her congenital deficiency of factor VII:C (table) diagnosed by chance. She had no history of haemorrhage or bruising; she had had uncomplicated tooth extractions, and her menstrual periods and deliveries had been normal. Her medical history was unremarkable except for high blood pressure (well controlled by altizide, spironolactone, and clonidine) and arthritis of the neck treated occasionally with aspirin. On Sept 29, 1983, she had a left-sided hemiparesis and was given dipyridamole. After 48 h she had recovered but examination revealed a right cervical murmur associated with mild stenosis of the right brachiocephalic arterial trunk. Echocardiography; Holter monitoring, and a cerebral scan were normal. Dipyridamole was continued, but on May 3, 1984, she had a further left-sided hemiparesis with altered consciousness. This disappeared in 10 days. Angiography demonstrated an atherosclerotic lesion 2 cm long with 20-30% stenosis at the origin of the brachiocephalic trunk. Treatment with flurbinprofen (100 mg per day) began on June 6, but because of side-effects it was replaced by aspirin (100 mg per day) on June 25. The Ivy bleeding-time was 10 min (normal 4-8 min) and the patient has been symptomless for 9 months. Her one brother is also factor VII deficient (10% of normal). Her three children are alive and well and there is no evidence of consanguinity in her family (a common finding in factor VII deficiency). Factor VII is a vitamin-K-dependent clotting factor. In the presence of tissue thromboplastin, activated proconvertin catalyses activation of the factor-X/factor-V/calcium/phospholipid complex. Factor VII deficiency is an autosomal recessive trait4 and is suspected if the prothrombin time is abnormal while the activated partial prothrombin time (APPT) is normal. These tests confirm the
1007 .TESTS OF HAEMOSTASIS
*Adrenahne induced
(May 5) and arachidonic acid induced (July 2). tBovme thromboplastin. tamidolytic method.
the intrinsic coagulation pathway and an abnormality of the extrinsic pathway. A functional assay for factor VII confirms the diagnosis. A very low level of factor VII prolongs the prothrombin time to within a range considered therapeutically desirable in the clinical use of vitamin K antagonists. Such a level would be expected to prevent thrombosis. However, deep-vein thrombosis and pulmonary emboli have been reported in patients with factor VII despite proconvertin levels as low as 14%,35%1, and less 5 than Our patient had two cerebrovascular strokes 6 months apart. These resolved completely and were presumably related to platelet emboli from an atheromatous plaque. Congenital deficiency of antithrombin III (100%) and protein C (94%) were ruled out. Venous thrombosis seems incompatible with a major coagulation factor defect but arterial thrombosis may not be prevented by a coagulation deficiency; rare cases of myocardial infarction have been reported in haemophiliacs.In atherogenesis coagulation may have a minor role compared with that of platelets. Aspirin therapy in such a patient may seem hazardous. Nevertheless, the risk of further cerebrovascular accidents in this patient cannot be ignored, and the normal Duke and only slightly prolonged Ivy bleeding times (table) when the patient was taking 100 mg aspirin daily are
integrity of
deficiency, 3%.
reassuring. JEAN-JACQUES LEFRERE Central Haematology
Laboratory,
Hôtel-Dieu, Paris; and Neurology Service,
Hôpital de la Pitié-Salpétrière, Paris
MARIE-PIERRE CHAUNU
JACQUELINE CONARD MARIE-HELENE HORELLOU MEYER SAMAMA
E, Gude JK Deep vein thrombosis and pulmonary embolism in congenital factor VII deficiency N Engl J Med 1973; 228: 141-42. Godal HC, Madsen K, Nissen-Meyer R. Thrombo-embolism in patients with total proconvertin (factor VII) deficiency. Acta Med Scand 1962; 171: 325-27. Shifter T, Mactey I, Creter D. Thromboembolism in congenital factor VII deficiency. Acta Haematol 1984; 71: 60-62. Mammen EF. Factor VII abnormalities. Sem Thrombos Hemost 1983; 9: 10-21. Hall CA, Rapaport SI, Ames SB, Degroot JA. A clinical and family study of hereditary proconvertin (Factor VII) deficiency Am J Med 1964; 37: 172-81. Borchgrevink CF. Myocardial infarction m a haemophiliac. Lancet 1959; i: 1229-30.
1. Gershwin 2. 3 4 5. 6
From 1964 to 1975, 200 patients were started on maintenance haemodialysis at this hospital,2 of whom 62 are known to be alive (29 on haemodialysis and 33 with a functioning renal transplant). Of these 62 patients, 3 have had severe calcific aortic stenosis. Patient 1 is a 57-year-old man who has been on haemodialysis for 12 years. 1 year ago he had worsening angina of effort associated with signs of significant aortic stenosis. Cardiac catheterisation revealed severe calcific aortic stenosis with minimal aortic regurgitation. 6 months ago an aortic valve was replaced and a heavily calcified tricuspid aortic valve of normal configuration was excised. He is currently well on twice weekly haemodialysis. Patient 2 is a 45-year-old man who started haemodialysis in 1973 for CRF due to chronic glomerulonephritis. In 1975 he received a renal transplant, but 6 months later was put back on haemodialysis. In 1978 signs of mild aortic stenosis were noted and 5 years later a two-dimensional echocardiogram revealed a calcified tricuspid aortic valve with slight calcification of the mitral valve annulus. Cardiac catheterisation in 1983 demonstrated calcific aortic stenosis with a gradient of 60 mm Hg across the valve. He is awaiting aortic valve replacement. Patient3 is a 53-year-old man who began haemodialysis in 1973 and received a successful renal transplant 2 years later. Renal transplant function was good until 1978, but has since gradually declined because of chronic rejection (current EDTA clearance 7 ml/min). In 1978 an aortic systolic murmur was noted and in 1981 an echocardiogram demonstrated aortic-valve calcification and’ thickened valve cusps with mild stenosis. In early 1985 cardiac catheterisation demonstrated severe calcific aortic stenosis, and shortly afterwards an aortic valve was successfully replaced. The aortic valve was tricuspid and appeared normal except for dense calcific deposits on the cusps. Calcification of a tricuspid aortic valve without inflammatory changes is usually seen in elderly patients.3 Our three patients had isolated aortic stenosis, with extracardiac metastatic calcification (periarticular in one and vascular in all three) and no history of rheumatic fever. Although these unusual findings might have occurred by chance an alternative interpretation is that the abnormal calcium-phosphate metabolism seen in CRF resulted in aortic-valve calcification (or accelerated the calcification of a susceptible valve). Mitral annulus calcification in haemodialysis patients has been linked with secondary hyperparathyroidism (two of our patients had had a parathyroidectomy), and aortic valve cusp thickening is more common in haemodialysis patients with mitral annulus calcification than in those without.’1 Since many haemodialysis patients have systolic murmurs, we may have underestimated the incidence of aortic-valvedisease in our haemodialysis patients, and a prospective echocardiographic study will be needed to determine if there is a real association between aortic-valve calcification and CRF. Department of Medicine, Charing Cross Hospital,
E. R. MAHER
London W6 8RF
J. R. CURTIS
MB, Virmani R, Robertson RM, Stone WJ. Mitral annular calcification in chronic renal failure. Chest 1984, 85: 367-71. 2. Henari FZ, Gower PE, Curtis JR, et al. Survival in 200 patients treated by HD and renal transplantation. Br Med J 1977; i: 409-12. 3. Pomerance A. Pathogenesis of aortic stenosis and relation to age. Br Heart J 1972; 34: 569-74 1. Forman
CALCIFIC AORTIC STENOSIS IN CHRONIC RENAL FAILURE
MAGNETIC RESONANCE IMAGING TO DETECT DEEP BASAL GANGLIA LESIONS IN HEMIDYSTONIA THAT ARE MISSED BY COMPUTERISED TOMOGRAPHY
SiR,-Your Sept 14 editorial suggests that some disorders may be associated with premature valve calcification and thus valve stenosis. Calcification of the mitral valve annulus is common in patients with chronic renal failure (CRF), occurs at a younger age than usual, and may cause functional mitral stenosis or regurgitation.’ Aortic-valve calcification is not recognised as a complication of CRF, but we have noted an unusual frequency of calcific aortic stenosis in patients with long-standing renal failure.
SIR,-Hemidystonia is often associated with computerised tomographic (CT) evidence of a lesion such as tumour, infarction, or haemorrhage in the contralateral basal ganglia and/or thalamus.l-4 However, even the most advanced CT scanner may fail to demonstrate a structural lesion in some cases of hemidystonia, even when secondary dystonia is suggested clinically. We describe here one patient in whom magnetic resonance imaging (MRI) demonstrated a large abnormality not visible on a CT scan.